The long-term objective of this project is to understand the regulation and function of gap junctional communication (GJC) during early embryonic development. This proposal aims to 1) determine whether beta-catenin regulates GJC, ii) investigate the regulation of GJC by analysis of the expression and localization of connexin-38 in normal and beta-catenin- deficient embryos, and iii) study the developmental function of connexin- 38 in the early embryo and investigate its role in cell adhesion. Gap junction regulation will be studied using the Xenopus embryonic model system. Maternal expression of beta-catenin or connexin-38 will be specifically blocked using anti-sense oligodeozynucleotides. GJC will be monitored by fluorescent dye microinjection and analysis of dye transfer between blastomeres of the early embryo. GJC is essential for normal heart development as transgenic mice lacking connexin-43 develop severe defects of the right ventricle (Reaume et al., 1995. Science 267: 1831). Patients with another development heart defect, visceroatrial heterotaxia show a high mutation rate in the connexin-43 gene (Britz-Cunningham et al., 1995. NEJM 332: 1323), while those exhibiting the X-linked neuropathy, Charcot-Marie-Tooth disease, have mutations in the connexin-32 gene (Bergoffer et al., Science 262: 2039). In addition, connexin-26 has been identified as a possible tumor suppressor, suggesting that gap junctional communication is involved in cell growth control (Lee et al., 1992. J. Cell Biol. 118: 1213). Given this relationship between normal development and junctional communication, an analysis of the regulation of gap junctions should lead to a better understanding of mechanisms which control normal growth and embryonic development.